Published in:
Open Access 01-08-2015 | Article
A systems view of type 2 diabetes-associated metabolic perturbations in saliva, blood and urine at different timescales of glycaemic control
Published in: Diabetologia | Issue 8/2015
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Aims/hypothesis
Metabolomics has opened new avenues for studying metabolic alterations in type 2 diabetes. While many urine and blood metabolites have been associated individually with diabetes, a complete systems view analysis of metabolic dysregulations across multiple biofluids and over varying timescales of glycaemic control is still lacking.
Methods
Here we report a broad metabolomics study in a clinical setting, covering 2,178 metabolite measures in saliva, blood plasma and urine from 188 individuals with diabetes and 181 controls of Arab and Asian descent. Using multivariate linear regression we identified metabolites associated with diabetes and markers of acute, short-term and long-term glycaemic control.
Results
Ninety-four metabolite associations with diabetes were identified at a Bonferroni level of significance (p < 2.3 × 10−5), 16 of which have never been reported. Sixty-five of these diabetes-associated metabolites were associated with at least one marker of glycaemic control in the diabetes group. Using Gaussian graphical modelling, we constructed a metabolic network that links diabetes-associated metabolites from three biofluids across three different timescales of glycaemic control.
Conclusions/interpretation
Our study reveals a complex network of biochemical dysregulation involving metabolites from different pathways of diabetes pathology, and provides a reference framework for future diabetes studies with metabolic endpoints.